Abstract
Administration of Escherichia coli endotoxin attenuates the ventilatory response to hypoxia (VRH) in newborn piglets, but the mechanisms responsible for this depression are not clearly understood. Nitric oxide (NO) production increases during sepsis and elevated NO levels can inhibit carotid body function. The role of endothelial NO on the VRH during endotoxemia was evaluated in 26 young rats. Minute ventilation (VE) and oxygen consumption (Vo2) were measured in room air (RA) and during 30 min of hypoxia (10% O2) before and after E. coli endotoxin administration. During endotoxemia, animals received placebo (PL, n = 8); a nonselective nitric oxide synthase (NOS) inhibitor (NG-nitro-L-arginine methyl ester, L-NAME, n = 9), or a neuronal NOS (nNOS) inhibitor (7-nitroindazole, 7-NI, n = 9). During endotoxemia, a larger increase in VE was observed only during the first min of hypoxia in the L-NAME group when compared with PL or 7-NI (p < 0.001). VRH was similar in the PL and 7-NI groups. A larger decrease in Vo2 at 30 min of hypoxia was observed in L-NAME and 7-NI groups when compared with PL (p < 0.03). These data demonstrate that the attenuation of the early VRH during endotoxemia is in part mediated by an inhibitory effect of endothelial NO on the respiratory control mechanisms.
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Abbreviations
- eNOS:
-
endothelial NOS
- L-NAME:
-
NG-nitro-L-arginine methyl ester
- nNOS:
-
neuronal NOS
- NO:
-
nitric oxide
- NOS:
-
nitric oxide synthase
- PL:
-
placebo
- RA:
-
room air
- RR:
-
respiratory rate
- 7-NI:
-
7-nitroindazole
- Tb:
-
body temperature
- VE:
-
minute ventilation
- VO2:
-
oxygen consumption
- VRH:
-
ventilatory response to hypoxia
- VT:
-
tidal volume
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Ladino, J., Bancalari, E. & Suguihara, C. Ventilatory Response to Hypoxia during Endotoxemia in Young Rats: Role of Nitric Oxide. Pediatr Res 62, 134–138 (2007). https://doi.org/10.1203/PDR.0b013e318098721a
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DOI: https://doi.org/10.1203/PDR.0b013e318098721a
